[Case of allergic bronchopulmonary aspergillosis complicated with lung abscess which developed into a bronchopleural fistula].

We report a case of bronchopleural fistula in a patient with allergic bronchopulmonary aspergillosis. A 25-year-old man was admitted with high fever and chest pain. Although his chest CT in a previous hospital showed pulmonary infiltrate suggesting the existence of a mucous plug, a mass shadow in the right upper lobe was recognized on admission to our hospital. Based on the presence of eosinophilia, elevated levels of total IgE and Aspergillus-specific IgE, positive precipitating antibody to Aspergillus, and detection of A. fumigatus in bronchial washing fluid, we diagnosed this case as ABPA complicated with lung abscess. Although we treated by antibiotics and antifungal drugs, the lung abscess did not improve and led to bronchopleural fistula. After addition of nebulised liposomal amphotericin B, his symptoms improved and treatment was successful.

Effect of procaterol, a beta(2) selective adrenergic receptor agonist, on airway inflammation and hyperresponsiveness.

BACKGROUND: beta-agonists are frequently used as bronchodilators for asthma as not only a reliever but also a controller, and their utility has increased with the development of long-acting beta(2) selective drugs. Although anti-inflammatory effects of beta(2) selective-agonists have been reported in vitro, side effects on augmentation of airway hyperresponsiveness by chronic use of beta(2) selective-agonists have been described in several reports. In this study, we investigated the effects of procaterol, a second-generation beta(2)-agonist, on airway inflammation in vivo using an antigen-specific murine model of asthma. METHODS: Mice immunized with ovalbumin (OVA) + alum and challenged with inhaled ovalbumin were orally administered procaterol during the challenge. After inhalation, the mice were tracheostomized and placed in a body box under controlled ventilation to measure airway resistance before and after acetylcholine inhalation. RESULTS: Administration of procaterol at a clinical dose equivalent did not augment airway hyperresponsiveness, inflammation of the airway wall, or subsequent airway wall thickening induced by OVA inhalation. BALF cell analysis revealed that the eosinophil number in the BALF was significantly reduced in procaterol-treated mice compared to untreated mice. CONCLUSIONS: Oral administration of procaterol at a clinical dose did not augment airway responsiveness, but did reduce eosinophil inflammation.

Silico-asbestosis that responded to steroid therapy.

A 73-year-old man with silico-asbestosis responded to steroid therapy. Chest CT scans showed diffuse micronodular opacities and ground glass opacities bilaterally throughout the entire lung fields, as well as progressive massive fibrosis in the bilateral upper lung fields. Diagnostic thoracoscopic biopsy revealed mixed dust pneumoconiosis with silicotic nodules, as well as fibrosis similar to that of Usual Interstitial Pneumonia (UIP) with many fibroblastic foci and alveolitis. Many asbestos bodies were also detected by iron staining.

Role of CCL21 and CCL19 in allergic inflammation in the ovalbumin-specific murine asthmatic model.

BACKGROUND: Dendritic cells are the most powerful of the antigen-presenting cells and are known to play important roles in sensitization and inflammation in allergen-specific asthma. Various cytokines and chemokines are involved in the maturation and activation of dendritic cells. Among them is CC chemokine ligand (CCL)21, a key chemokine in the entry of naive T cells and antigen-stimulated dendritic cells into the T-cell zones of secondary lymphoid organs, which is a critical process in antigen-specific T-cell activation. OBJECTIVE: We studied the role of CCL21 in airway inflammation in asthma by using BALB/c-plt/plt (plt) mice, which possess genetic defects in expression of both CCL21 and CCL19. METHODS: Plt and control BALB/c mice were immunized with ovalbumin and alum 4 times and thereafter were subjected to a 2-week regimen of ovalbumin inhalation. RESULTS: In plt mice, ovalbumin-specific IgE response was delayed compared with control BALB/c mice, but they had the same level of response after final immunization. Although airway inflammation and response to acetylcholine were significantly reduced compared with BALB/c mice, significant eosinophilic inflammation and hyperresponsiveness were also observed in plt mice after 2 weeks of inhalation. Four weeks after cessation of inhalation, airway inflammation and hyperresponsiveness in plt mice were greater than in BALB/c mice. At the time of resolution of airway inflammation, IL-10 production was enhanced in BALB/c mice but not in plt mice. CONCLUSION: The chemokines CCL21 and CCL19 were critical for resolution of airway inflammation. CLINICAL IMPLICATIONS: The findings about the chemokines for induction and resolution of inflammation are key to establishing a new strategy for asthma immunotherapy.

Involvement of GATA-3-dependent Th2 lymphocyte activation in airway hyperresponsiveness.

The pathophysiological characteristics of bronchial asthma consist of chronic inflammation of airways, airway hyperresponsiveness, and bronchoconstriction. Studies have shown that T helper type 2 (Th2) cytokines produced by both T cells and mast cells in the airway contribute substantially to the initiation of inflammation in both experimental and human bronchial asthma. GATA-3 is a transcription factor essential to the production of Th2 cytokines by T lymphocytes. To clarify the role of GATA-3-expressing T cells in the pathophysiology of bronchial asthma, we utilized transgenic (Tg) mice carrying the GATA-3 gene and the ovalbumin (OVA)-specific T cell receptor gene (GATA-3-Tg/OVA-Tg). Mice were intranasally administrated OVA without systemic immunization. Airway responses were analyzed with noninvasive and invasive whole body plethysmographs. GATA-3-Tg/OVA-Tg mice exhibited significantly higher IL-13 and IL-4 protein expression in the airway. Although there were no differences in the types of infiltrating cells between GATA-3-Tg/OVA-Tg and GATA-3-non-Tg/OVA-Tg mice and no significant increase in IgE level in either group compared with nontreated mice, the response after ACh inhalation was significantly elevated in GATA-3-Tg/OVA-Tg on the seventh day of intranasal treatment with OVA. This hyperresponsiveness was inhibited by 5-lipoxygenase inhibitor and IL-13 neutralization, suggesting that airway responses were induced through IL-13 and leukotriene pathway. In conclusion, airway hyperresponsiveness, a characteristic of bronchial asthma, is regulated at the level of GATA-3 transcription by T lymphocytes in vivo.

Characterization of the replication region of plasmid pLS32 from the Natto strain of Bacillus subtilis.

Plasmid pL32 from the Natto strain of Bacillus subtilis belongs to a group of low-copy-number plasmids in gram-positive bacteria that replicate via a theta mechanism of replication. We studied the DNA region encoding the replication protein, RepN, of pLS32, and obtained the following results. Transcription of the repN gene starts 167 nucleotides upstream from the translational start site of repN. The copy number of repN-coding plasmid pHDCS2, in which the repN gene was placed downstream of the IPTG (isopropyl-1-thio-beta-D-galactopyranoside)-inducible Pspac promoter, was increased 100 fold by the addition of IPTG. Histidine-tagged RepN bound to a specific region in the repN gene containing five 22-bp tandem repeats (iterons) with partial mismatches, as shown by gel retardation and foot printing analyses. Sequence alterations in the first three iterons resulted in an increase in plasmid copy number, whereas those in either the forth or fifth iteron resulted in the failure of plasmid replication. The iterons expressed various degrees of incompatibility with an incoming repN-driven replicon pSEQ243, with the first three showing the strongest incompatibility. Finally, by using a plasmid, pHDMAEC21, carrying the sequence alterations in all the five iterons in repN and thus unable to replicate but encoding intact RepN, the region necessary for replication was confined to a 96-bp sequence spanning the 3'-terminal half of the fourth iteron to an A+T-rich region located downstream of the fifth iteron. From these results, we conclude that the iterons in repN are involved in both the control of plasmid copy number and incompatibility, and we suggest that the binding of RepN to the last two iterons triggers replication by melting the A+T-rich DNA sequence.